and the results can be used for comparison between the
immobilized catalysts. The homogeneous Rh2(S-MEPY)4 (5)
gives a diastereomeric ratio of 1.3:1 (trans 58% ee:cis 33%
ee) and 59% yield (Figure 1).1c Previously, Doyle’s co-
valently bound Rh2(S-MEPY)4 catalyst on solid support
showed an improvement in the overall stereoselectivity in
this reaction, as the product was formed in a 2.1:1 mixture
of diastereomers favoring the trans isomer (trans 66% ee:
cis 49% ee).6c In contrast, noncovalently bound 9a-Rh2(S-
MEPY)4 gives the product as a 1:1 mixture of diastereomers
(trans 42% ee:cis 31% ee) (eq 1). These results indicate that
the noncovalent immobilization strategy has a minimal effect
on the chiral environment around the immobilized catalysts,
as results similar to those found for the homogeneous catalyst
are obtained.
diazoacetates such as 14.7 When 2 mol % immobilized 9a-
Rh2(S-MEPY)4 was used, allyl diazoacetate 14 underwent
highly enantioselective intramolecular cyclopropanation to
give product 15 in 81% yield and 95% ee (Table 4). The
Table 4. Asymmetric Intramolecular Cyclopropanation of Allyl
Diazoacetate 14 Using Immobilized Catalyst
a
9a-Rh2(S-MEPY)4
a Homogeneous reaction: 79% yield, 95% ee. Reported reaction (ref
7): 75% yield, 95% ee.
The best assessment of this immobilization technology
would be to evaluate the immobilized catalysts in reactions
in which their homogeneous counterparts routinely give high
asymmetric induction. Therefore, a few of the best applica-
tions of these catalysts that have been reported in the
literature were chosen and repeated using the homogeneous
catalysts. Since catalysts 3 and Rh2(R-BNP)4 (8) have not
been reported to give enantioselectivities >85%, they were
further tested in the asymmetric cyclopropanation of styrene
with methyl phenyldiazoacetate (10). The catalysts were
recycled five times, and the reaction time and enantioselec-
tivity was recorded for every other cycle. Interestingly, in
both these systems the enantioselectivity was maintained with
minimal loss compared to the first cycle (Table 3).
catalyst was recycled three times with virtually no loss in
enantioselectivity. The enantioselectivity is identical to the
homogeneous control and reported homogeneous reactions.
Oxazetidinone-based catalysts such as Rh2(S-MEAZ)4 (6)
have been very successful for reactions with acceptor/
acceptor- and donor/acceptor-substituted carbenoids.8 The
best application of Rh2(S-MEAZ)4 is the intramolecular
cyclopropanation of phenyldiazoacetate 16 to give the
cyclopropane lactone 17.8 In the presence of immobilized
9a-Rh2(S-MEAZ)4 (2 mol %), the cyclopropane product is
formed in 80% yield and 88% ee (Table 5). The enantiose-
lectivity in the initial cycle is comparable to that of the
homogeneous control reaction (86% ee) and the reported
homogeneous reaction (84% ee). Recycling the catalyst
showed that after three reaction cycles, the enantioselectivity
gradually drops to 70% ee.
One of the most notable examples of the enantioselective
reactions of the Rh2(S-PTTL)4 catalyst is the intramolecular
C-H activation of substituted aryldiazoacetates such as 18
to form dihydrobenzofurans.9 Recently, Fukuyama and co-
workers used a similar C-H activation reaction as the key
step in the total synthesis of (-)-ephedradine A.10 The room-
temperature reaction using Rh2(S-PTTL)4 in the intramo-
lecular C-H activation of aryldiazoacetate 18 has been
reported in hexane, giving 19 in 78% yield, 99:1 dr, and
70% ee.9 Conducting the reaction in toluene with homoge-
Table 3. Asymmetric Cyclopropanation of Styrene with
Methyl Phenyldiazoacetate (10) Using Immobilized Catalysts
a
9a-3 and 9a-Rh2(R-BNP)4
9a-3
time (min)
9a-Rh2(R-BNP)4
cycle
ee (%)
time (min)
ee (%)
1
3
5
12
15
25
53
50
48
15
30
60
40
39
38
(7) Doyle, M. P.; Austin, R. E.; Bailey, A. S.; Dwyer, M. P.; Dyatkin,
A. B.; Kalinin, A. V.; Kwan, M. M. Y.; Liras, S.; Oalmann, C. J.; Pieters,
R. J.; Protopopova, M. N.; Raab, C. E.; Roos, G. H. P.; Zhou, Q.-L.; Martin,
S. F. J. Am. Chem. Soc. 1995, 117, 5763.
1
a Reaction yields determined by H NMR, using DMAP as the internal
standard, or isolated yields; in all cases, values were greater than 70%. See
Experimental Section.
(8) Doyle, P. M.; Davies, B. S.; Hu, W. Org. Lett. 2000, 2, 1145.
(9) Saito, H.; Oishi, H.; Kitagaki, S.; Nakamura, S.; Anada, M.;
Hashimoto, S. Org. Lett. 2002, 4, 3887.
(10) (a) Kurosawa, W.; Kan, T.; Fukuyama, T. J. Am. Chem. Soc. 2003,
125, 8112. (b) Kurosawa, W.; Kan, T.; Fukuyama, T. Synlett 2003, 1028.
One of the earliest applications of the Rh2(S-MEPY)4
catalyst was the intramolecular cyclopropanation of allyl
Org. Lett., Vol. 7, No. 14, 2005
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